Ketoconazole-associated hepatic injury

Stricker, Bruno H. Ch.; Blok, A. P. R.; Bronkhorst, Frans; Parys, G.E. Van; Desmet, V J

doi:10.1016/s0168-8278(86)80495-0

Cited by 118 publications

(18 citation statements)

References 17 publications

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“…Some authors suggest the true incidence is closer to 1 in 2000. 62 The incidence of liver injury with the newer imadazoles and allyamines is lower 59 and, given the short duration of treatment in skin infections, it should not be a prohibitive factor in the use of oral antifungal agents. Typical dosing schedules for tinea corporis or cruris are fluconazole 150 mg once per week for 3 weeks, itraconazole 200 mg per day for 2 weeks, or terbinafine 250 mg per day for 2 weeks.…”

Section: Abscess Furuncles Carbunclesmentioning

confidence: 99%

Skin Conditions in the Athlete

2008

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Dermatologic conditions are a common presenting complaint in the athletic training room. There are many different causes for rashes, and treatment options vary depending on the condition and the severity. Bacterial infections of the skin have a variety of different appearances and can spread rapidly among individuals. Healthcare providers need to be aware of the increasing prevalence of methicillin-resistant Staphylococcus aureus when making the choice of antibiotics. Other infectious rashes, including tinea and herpes, are well-described conditions in wrestlers; however, these rashes can be seen in any athlete, especially those engaged in contact sports. Early recognition and appropriate treatment are important to clear the rash and reduce the spread to others. In addition to infectious rashes, athletes are prone to mechanical rashes and skin conditions due to friction and tight-fitting equipment. Sports medicine providers must not only diagnose and treat these conditions but also be aware of the return-to-play guidelines set forth by the governing bodies under which he or she operates.

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Section: Abscess Furuncles Carbunclesmentioning

confidence: 99%

Skin Conditions in the Athlete

2008

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“…KET also inhibits the synthesis of testosterone in both testicular and adrenal cells and therefore is used for treatment of androgen-dependent diseases such as advanced prostate cancer [2]. Despite the wide and frequent use of KET, there is much evidence of hepatotoxicity and hepatic tumors associated with it [3]–[5]. KET is extensively metabolized by the hepatic biotransformation enzymes [6].…”

Section: Introductionmentioning

confidence: 99%

Enantiospecific Effects of Ketoconazole on Aryl Hydrocarbon Receptor

et al. 2014

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Azole antifungal ketoconazole (KET) was demonstrated to activate aryl hydrocarbon receptor (AhR). Since clinically used KET is a racemic mixture of two cis-enantiomers (2R,4S)-(+)-KET and (2S,4R)-(−)-KET, we examined the effects of KET enantiomers on AhR signaling pathway. (+)-KET dose-dependently activated AhR in human gene reporter cell line AZ-AHR, and displayed 5–20× higher agonist activity (efficacy), as compared to (−)-KET; both enantiomers were AhR antagonists with equal potency (IC50). Consistently, (+)-KET strongly induced CYP1A1 mRNA and protein in human HepG2 cells, while (−)-KET exerted less than 10% of (+)-KET activity. In primary human hepatocytes, both enantiomers preferentially induced CYP1A2 over CYP1A1 mRNA and protein, and the potency of (+)-KET was slightly higher as compared to (−)-KET. Ligand binding assay with guinea pig liver cytosols revealed that both (+)-KET and (−)-KET are weak ligands of AhR that displaced [3H]-TCDD with comparable potency. Similarly, both enantiomers weakly transformed AhR to DNA-binding form with similar potency, as showed by EMSA, in guinea pig liver cytosolic extracts and nuclear extracts from mouse Hepa-1 cells. We also examined effects of KET on glucocorticoid receptor (GR), a regulator of AhR activity. Both KET enantiomers antagonized GR with similar potency, as revealed by gene reporter assay in AZ-GR cell line and down-regulation of tyrosine aminotransferase mRNA in human hepatocytes. Finally, we demonstrate enantiospecific antifungal activities of KET enantiomers in six Candida spp. strains. In conclusion, the significance of current study is providing the first evidence of enatiospecific effects of cis-enantiomers of ketoconazole on AhR-CYP1A pathway.

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“…Despite having good efficacy both as a steroidogenesis inhibitor and antifungal agent, the reported adverse reactions associated with its use have raised safety concerns. The estimated incidence rate of symptomatic ketoconazole-induced hepatotoxicity varies from as low as 0.007% (5) to as high as 0.05% (6) and 0.2% (7). Other adverse effects reported with ketoconazole use include gastrointestinal complaints (such as nausea, vomiting, abdominal pain, and anorexia), adrenal insufficiency, skin rash, pruritus, and drug-drug interactions (8).…”

Section: Discussionmentioning

confidence: 99%

Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing’s Disease: A Case Report

Chai

Tajuddin

Wahab

et al. 2018

Int J Endocrinol Metab

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IntroductionKetoconazole has long been the first-line medical therapy for controlling hypercortisolism secondary to either pituitary or adrenal pathology. However, it is largely unavailable in most countries. As a result, we have turned to fluconazole as a viable alternative in view of its favourable safety profile.Case PresentationA 50-year-old lady developed recurrent Cushing’s disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review.ConclusionsThis case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease.

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Ketoconazole-associated hepatic injury

Cited by 118 publications

References 17 publications

Skin Conditions in the Athlete

Skin Conditions in the Athlete

Enantiospecific Effects of Ketoconazole on Aryl Hydrocarbon Receptor

Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing’s Disease: A Case Report

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